Follistatin gene delivery enhances muscle growth and strength in nonhuman primates

Janaiah Kota, Chalonda R. Handy, Amanda M. Haidet, Chrystal L. Montgomery, Amy Eagle, Louise R. Rodino-Klapac, Danielle Tucker, Christopher J. Shilling, Walter R. Therlfall, Christopher M. Walker, Steven E. Weisbrode, Paul M L Janssen, K. Reed Clark, Zarife Sahenk, Jerry R. Mendell, Brian K. Kaspar

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Antagonists of myostatin, a blood-borne negative regulator of muscle growth produced in muscle cells, have shown considerable promise for enhancing muscle mass and strength in rodent studies and could serve as potential therapeutic agents for human muscle diseases. One of the most potent of these agents, follistatin, is both safe and effective in mice, but similar tests have not been performed in nonhuman primates. To assess this important criterion for clinical translation, we tested an alternatively spliced form of human follistatin that affects skeletal muscle but that has only minimal effects on nonmuscle cells. When injected into the quadriceps of cynomolgus macaque monkeys, a follistatin isoform expressed from an adeno-associated virus serotype 1 vector, AAV1-FS344, induced pronounced and durable increases in muscle size and strength. Long-term expression of the transgene did not produce any abnormal changes in the morphology or function of key organs, indicating the safety of gene delivery by intramuscular injection of an AAV1 vector. Our results, together with the findings in mice, suggest that therapy with AAV1-FS344 may improve muscle mass and function in patients with certain degenerative muscle disorders.

Original languageEnglish (US)
Article number6ra15
JournalScience Translational Medicine
Volume1
Issue number6
DOIs
StatePublished - Nov 11 2009
Externally publishedYes

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Follistatin
Muscle Strength
Primates
Muscles
Growth
Myostatin
Genes
Dependovirus
Macaca fascicularis
Intramuscular Injections
Macaca
Muscular Diseases
Transgenes
Muscle Cells
Rodentia
Protein Isoforms
Skeletal Muscle
Safety
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kota, J., Handy, C. R., Haidet, A. M., Montgomery, C. L., Eagle, A., Rodino-Klapac, L. R., ... Kaspar, B. K. (2009). Follistatin gene delivery enhances muscle growth and strength in nonhuman primates. Science Translational Medicine, 1(6), [6ra15]. https://doi.org/10.1126/scitranslmed.3000112

Follistatin gene delivery enhances muscle growth and strength in nonhuman primates. / Kota, Janaiah; Handy, Chalonda R.; Haidet, Amanda M.; Montgomery, Chrystal L.; Eagle, Amy; Rodino-Klapac, Louise R.; Tucker, Danielle; Shilling, Christopher J.; Therlfall, Walter R.; Walker, Christopher M.; Weisbrode, Steven E.; Janssen, Paul M L; Clark, K. Reed; Sahenk, Zarife; Mendell, Jerry R.; Kaspar, Brian K.

In: Science Translational Medicine, Vol. 1, No. 6, 6ra15, 11.11.2009.

Research output: Contribution to journalArticle

Kota, J, Handy, CR, Haidet, AM, Montgomery, CL, Eagle, A, Rodino-Klapac, LR, Tucker, D, Shilling, CJ, Therlfall, WR, Walker, CM, Weisbrode, SE, Janssen, PML, Clark, KR, Sahenk, Z, Mendell, JR & Kaspar, BK 2009, 'Follistatin gene delivery enhances muscle growth and strength in nonhuman primates', Science Translational Medicine, vol. 1, no. 6, 6ra15. https://doi.org/10.1126/scitranslmed.3000112
Kota, Janaiah ; Handy, Chalonda R. ; Haidet, Amanda M. ; Montgomery, Chrystal L. ; Eagle, Amy ; Rodino-Klapac, Louise R. ; Tucker, Danielle ; Shilling, Christopher J. ; Therlfall, Walter R. ; Walker, Christopher M. ; Weisbrode, Steven E. ; Janssen, Paul M L ; Clark, K. Reed ; Sahenk, Zarife ; Mendell, Jerry R. ; Kaspar, Brian K. / Follistatin gene delivery enhances muscle growth and strength in nonhuman primates. In: Science Translational Medicine. 2009 ; Vol. 1, No. 6.
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